abstract
Objective: To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1. Methods: A single nucleotide polymorphism of ABCB1 3435C>T (rs1045642) in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment. Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration. The relationship between plasma efavirenz concentrations and ABCB1 3435C>T polymorphisms was analyzed. Results: Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age, gender, body weight, CD4 count and plasma HIV-1 RNA, blood biochemical parameters, antiretroviral duration or ABCB1 3435C>T polymorphisms, except for height (OR=0.902, 95% CI: 0.835-0.973) (P<0.05). The minor allele frequency of ABCB1 3435C>T was 0.446. The frequency of the heterozygous mutant ABCB1 3435C/ T was 53.02% (n=79), ABCB1 3435T/T homozygous mutant was 18.12% (n=27) and the wild type ABCB1 3435C/C genotype was 28.86% (n=43). The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L [IQR: (1.46-4.12) mg/L]. The plasma concentration of efavirenz was higher in cases with ABCB1 3435T/T homozygous mutant [2.73 mg/L, IQR: (2.02-4.19) mg/L] and ABCB1 3435C/T heterozygous mutant [2.29 mg/L, IQR: (1.41-4.28) mg/L] genotypes compared to the wild type ABCB1 3435C/C homozygous [2.1 mg/L, IQR: (1.37-3.53) mg/L]. However, there was no statistically significant difference in the efavirenz concentration between the different genotypes (P>0.05). Conclusions: There is no statistical significance for a tendency toward higher plasma efavirenz concentration in the ABCB1 3435T/T and ABCB1 3435C/T genotypes. No parameters of physiological characteristics in this study except for height were found to be predictors of high plasma efavirenz concentration in Thai HIV-1 infected cases.
keywords
P-GLYCOPROTEIN; C3435T MUTATION; MDR1 GENE; CYP2B6; EXPRESSION; PHARMACOKINETICS; PHARMACOGENETICS; FREQUENCY; CANCER; ABCC2
subject category
Public, Environmental & Occupational Health; Tropical Medicine
authors
Barusrux, S; Koomdee, N; Sukprasong, R; Manosuthi, W; Chamnanphon, M; Puangpetch, A; Sukasem, C; Nissapatorn, V; Pereira, MD
our authors
Maria de Lourdes Gomes Pereira
Associate Professor with Aggregationacknowledgements
This work was supported by Mahidol University, Thailand Research Fund, Thailand Office of the Higher Education Commission under New Researchers Grant (MRG 5480136), the project CICECO-Aveiro Institute of Materials, national funds through the FCT/MCTES (FCT Ref. UID/CTM/50011/2019) and Rachadapisek Sompote Fund for Postdoctoral Fellowship, Chulalongkorn University. We are grateful to the Institute of Infectious Diseases of Bamrasnaradura, the Ministry of Public Health, Thailand and all participants who contributed to the study.